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Astatine-211-labele...
Astatine-211-labeled antibodies for treatment of disseminated ovarian cancer: an overview of results in an ovarian tumor model
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- Andersson, Håkan, 1944 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för särskilda specialiteter, Avdelningen för onkologi,Institute of Selected Clinical Sciences, Department of Oncology
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- Elgqvist, Jörgen, 1963 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för särskilda specialiteter, Avdelningen för radiofysik,Institute of Selected Clinical Sciences, Department of Radiation Physics
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- Horvath, György, 1942 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för särskilda specialiteter, Avdelningen för onkologi,Institute of Selected Clinical Sciences, Department of Oncology
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- Hultborn, Ragnar, 1946 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för särskilda specialiteter, Avdelningen för onkologi,Institute of Selected Clinical Sciences, Department of Oncology
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- Jacobsson, Lars, 1947 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för särskilda specialiteter, Avdelningen för radiofysik,Institute of Selected Clinical Sciences, Department of Radiation Physics
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Jensen, H. (author)
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- Karlsson, Börje (author)
- Gothenburg University,Göteborgs universitet,Institutionen för särskilda specialiteter, Avdelningen för radiofysik,Institute of Selected Clinical Sciences, Department of Radiation Physics
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- Lindegren, Sture, 1960 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för särskilda specialiteter, Avdelningen för radiofysik,Institute of Selected Clinical Sciences, Department of Radiation Physics
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- Palm, Stig, 1964 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för särskilda specialiteter, Avdelningen för radiofysik,Institute of Selected Clinical Sciences, Department of Radiation Physics
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(creator_code:org_t)
- 2003
- 2003
- English.
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In: Clin Cancer Res. - 1078-0432. ; 9:10 Pt 2
- Related links:
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https://gup.ub.gu.se...
Abstract
Subject headings
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- PURPOSE: The aim of the study was to establish and refine a preclinical model to alpha-immunoradiotherapy of ovarian cancer. EXPERIMENTAL DESIGN: At-211 was produced by cyclotron irradiation of a bismuth-209 target and isolated using a novel dry distillation procedure. Monoclonal antibodies were radiohalogenated with the intermediate reagent N-succinimidyl 3-(trimethylstannyl)benzoate and characterized in terms of radiochemical yield and in vitro binding properties. In vitro OVCAR-3 cells were irradiated using an external Cobalt-60 beam, as reference, or At-211-albumin and labeled antibody. Growth assays were used to establish cell survival. A Monte Carlo program was developed to simulate the energy imparted and the track length distribution. Nude mice were used for studies of WBC depression, with various activities of Tc-99m antibodies, as reference, and At-211 antibodies. In efficacy studies, OVCAR-3 cells were inoculated i.p., and animals were treated 2 weeks later. The animals were either dissected 6 weeks later or followed-up for long-term survival. RESULTS: A rapid distillation procedure, as well as a rapid and high-yield, single-pot labeling procedure, was achieved. From growth inhibition data, the relative biological effectiveness of the alpha-emission for OVCAR-3 cells was estimated to be approximately 5, which is in the same range as found in vivo for hematological toxicity. At-211 MOv18 was found to effectively inhibit the development of tumors and ascites, also resulting in long-term survival without significant toxic effect. CONCLUSIONS: Use of the short-range, high-linear energy transfer alpha-emitter At-211 conjugated to a surface epitope-recognizing monoclonal antibody appears to be highly efficient without significant toxicity in a mouse peritoneal tumor model, urging a Phase I clinical trial.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- Animals
- Antibodies
- Monoclonal/therapeutic use
- Astatine/*therapeutic use
- Benzoates/therapeutic use
- Cell Division
- Cell Line
- Tumor
- Cell Survival
- Clinical Trials
- Dose-Response Relationship
- Radiation
- Female
- Humans
- Isotopes/*therapeutic use
- Mice
- Mice
- Inbred BALB C
- Mice
- Nude
- Monte Carlo Method
- Neoplasm Transplantation
- Ovarian Neoplasms/*radiotherapy
- Radioimmunotherapy/*methods
- Radiometry
- Time Factors
- Tissue Distribution
- Trimethyltin Compounds/therapeutic use
Publication and Content Type
- ref (subject category)
- art (subject category)
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Andersson, Håkan ...
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Elgqvist, Jörgen ...
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Horvath, György, ...
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Hultborn, Ragnar ...
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Jacobsson, Lars, ...
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Jensen, H.
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Karlsson, Börje
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Lindegren, Sture ...
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Palm, Stig, 1964
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
- Articles in the publication
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Clin Cancer Res
- By the university
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University of Gothenburg